Antimicrobial Drugs and Microbial Diseases of the Skin and Eyes: Study Notes

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Antimicrobial Drugs

Introduction to Chemotherapy and Antimicrobial Drugs

Chemotherapy refers to the use of chemicals to treat diseases, particularly infections caused by microorganisms. Antimicrobial drugs include antibiotics (produced by microbes) and synthetic compounds that inhibit or kill pathogens. The concept of selective toxicity is central, meaning the drug targets the pathogen without harming the host.

Antibiotic: Substance produced by a microbe that inhibits other microbes.
Antimicrobial drug: Synthetic or natural substance that interferes with microbial growth.
Spectrum of activity: Narrow-spectrum drugs target specific groups; broad-spectrum drugs affect a wide range of microbes.
Superinfection: Overgrowth of resistant normal microbiota due to antibiotic use.

Spectrum of Activity of Antibiotics and Other Antimicrobial Drugs

Mechanisms of Antimicrobial Action

Antimicrobial drugs act through several mechanisms to inhibit or kill microbes:

Bactericidal: Kill microbes directly.
Bacteriostatic: Inhibit microbial growth, allowing the immune system to eliminate the pathogen.

Mnemonic for bacteriostatic and bactericidal antibiotics

Major Mechanisms of Action

Inhibition of cell wall synthesis: e.g., penicillins, cephalosporins, bacitracin, vancomycin.
Inhibition of protein synthesis: e.g., chloramphenicol, erythromycin, tetracyclines, streptomycin.
Inhibition of nucleic acid replication and transcription: e.g., quinolones, rifampin.
Injury to plasma membrane: e.g., polymyxin B.
Inhibition of essential metabolite synthesis: e.g., sulfanilamide, trimethoprim.

Mechanisms of antimicrobial action on bacterial cell

Inhibitors of Cell Wall Synthesis

These drugs prevent the synthesis of peptidoglycan, weakening the cell wall and causing cell lysis, especially in Gram-positive bacteria.

Penicillins: Contain a β-lactam ring; prevent cross-linking of peptidoglycans.
Cephalosporins: Similar to penicillins but with a different β-lactam ring structure.
Polypeptide antibiotics: Bacitracin (topical), vancomycin (last line against MRSA).
Antimycobacterial antibiotics: Isoniazid and ethambutol target mycolic acid synthesis in Mycobacterium.

Structures of natural and semisynthetic penicillins TEM of Gram-positive bacterium lysing after penicillin treatment Comparison of cephalosporin and penicillin nuclei Penicillinase action on penicillin Structure of acid-fast cell wall in Mycobacterium

Inhibitors of Protein Synthesis

These drugs target bacterial 70S ribosomes, interfering with translation and protein production.

Chloramphenicol: Inhibits peptide bond formation at the 50S subunit; broad spectrum but can suppress bone marrow.
Aminoglycosides: Change the shape of the 30S subunit, causing misreading of mRNA (e.g., streptomycin, gentamicin).
Tetracyclines: Block tRNA attachment to the ribosome; broad spectrum, effective against intracellular pathogens.
Macrolides: Contain a macrocyclic lactone ring; e.g., erythromycin, effective against Gram-positive bacteria.

Mechanisms of protein synthesis inhibition by antibiotics Structure of chloramphenicol Structure of tetracycline Structure of erythromycin

Inhibitors of Nucleic Acid Synthesis

These drugs interfere with DNA replication or transcription, targeting enzymes like DNA gyrase or RNA polymerase.

Rifamycins: Inhibit mRNA synthesis; used for tuberculosis and leprosy.
Quinolones/Fluoroquinolones: Inhibit DNA gyrase; broad spectrum (e.g., ciprofloxacin).

Mechanisms of nucleic acid synthesis inhibition

Inhibitors of Essential Metabolite Synthesis

These drugs act as antimetabolites, competing with normal substrates for bacterial enzymes. A classic example is the inhibition of folic acid synthesis.

Sulfonamides: Inhibit the enzyme for PABA production, blocking folic acid synthesis. Humans are unaffected because they obtain folic acid from their diet.
Trimethoprim: Often used in combination with sulfonamides for synergistic effect.

Pathway of folic acid synthesis and inhibition by sulfonamides and trimethoprim

Antifungal Drugs

Fungi are eukaryotes, making selective toxicity more challenging. Antifungal drugs target unique fungal structures such as ergosterol in membranes or β-glucan in cell walls.

Polyenes (e.g., amphotericin B): Bind to ergosterol, forming pores in the membrane.
Azoles: Inhibit ergosterol synthesis (e.g., imidazoles, triazoles).
Echinocandins: Inhibit β-glucan synthesis in the cell wall.
Flucytosine: Inhibits nucleic acid synthesis.
Griseofulvin: Inhibits microtubule formation, used for dermatophyte infections.

Fungal cell structure and antifungal drug targets Diagram of antifungal drug mechanisms

Antiviral, Antiprotozoan, and Antihelminthic Drugs

Antiviral drugs are fewer due to the challenge of targeting viruses without harming host cells. They may inhibit viral entry, uncoating, nucleic acid synthesis, or release. Antiprotozoan and antihelminthic drugs target unique aspects of these eukaryotic pathogens.

Antiviral: Acyclovir (herpes), inhibitors of reverse transcriptase (HIV), protease inhibitors, integrase inhibitors.
Antiprotozoan: Quinine, chloroquine (malaria), metronidazole (anaerobic protozoa).
Antihelminthic: Niclosamide (tapeworms), mebendazole (intestinal helminths), ivermectin (roundworms).

Testing Antimicrobial Efficacy

Laboratory methods are used to determine the effectiveness of antimicrobial drugs against specific pathogens.

Kirby-Bauer disk diffusion test: Measures the zone of inhibition around antibiotic disks on an agar plate.
E test: Determines the minimal inhibitory concentration (MIC).
Broth dilution test: Determines MIC and minimal bactericidal concentration (MBC).

Kirby-Bauer disk diffusion test

Antimicrobial Resistance

Resistance arises through genetic changes and is often spread via plasmids or transposons. Mechanisms include enzymatic drug inactivation, alteration of target sites, decreased permeability, and increased efflux.

Superbugs: Bacteria resistant to multiple antibiotics.
Persister cells: Survive antibiotic treatment due to genetic traits.

Antibiotic Misuse and Safety

Misuse of antibiotics accelerates resistance. Safety considerations include the therapeutic index (risk vs. benefit), drug interactions, and potential organ toxicity.

Synergism: Combined effect of drugs is greater than individual effects.
Antagonism: Combined effect is less than individual effects.

Microbial Diseases of the Skin and Eyes

Skin: Properties and Defenses

The skin is a physical and chemical barrier to infection. Its dryness, saltiness, low pH, and presence of lysozyme inhibit microbial growth. Normal microbiota include Gram-positive, salt-tolerant bacteria such as Staphylococcus, Micrococcus, and diphtheroids.

Common Signs and Symptoms of Skin Infections

Exanthem: Skin rash from disease.
Enanthem: Rash on mucous membranes (e.g., inside the mouth).
Lesions: Fluid-filled areas, often containing pus (dead leukocytes, protein, debris).

Bacterial Infections of the Skin

Staphylococcus

Staphylococcus epidermidis: Normal flora, opportunistic.
Staphylococcus aureus: Pathogenic, produces toxins (leukocidins, hemolysins, exfoliative toxin, enterotoxins), causes scalded skin syndrome, toxic shock syndrome, and impetigo. MRSA is a major concern in hospitals and communities.

Streptococcus

Streptococcus pyogenes (GAS): Beta-hemolytic, produces M protein (antiphagocytic), streptokinases, hyaluronidase, and superantigens. Causes erysipelas, impetigo, and necrotizing fasciitis.

Pseudomonas

Pseudomonas aeruginosa: Gram-negative, produces blue-green pus, associated with swimmer's ear and post-burn infections.

Propionibacterium

Propionibacterium acnes: Causes acne by metabolizing sebum; treated with antibiotics, benzoyl peroxide, or blue light.

Viral Infections of the Skin

Human papillomaviruses (HPV): Cause warts; some types linked to cancer.
Poxviruses: Smallpox (eradicated), monkeypox (zoonotic).
Herpesviruses: HSV-1 (oral), HSV-2 (genital), varicella-zoster (chickenpox, shingles), can cause latent infections.
Measles (rubeola): Causes Koplik's spots, macular rash, immune amnesia; prevented by MMR vaccine.
Rubella (German measles): Milder rash, can cause congenital defects.
Parvovirus B19: Fifth disease (slapped cheek).
Roseola (HHV-6, HHV-7): High fever, rash.

Fungal Infections of the Skin

Cutaneous mycoses (dermatophytes): Cause ringworm (tinea) of skin, hair, nails. Genera include Trichophyton, Epidermophyton, Microsporum. Treated with griseofulvin or topical azoles.

Ringworm (tinea) on skin

Subcutaneous mycoses: Sporothrix schenckii causes sporotrichosis (rose handler's disease).
Candidiasis: Candida albicans causes thrush and yeast infections, especially after antibiotic use or in immunosuppression.

Fungal infection between toes (athlete's foot)

Arthropod Infections

Scabies: Caused by Sarcoptes scabiei mite; intense itching, rash; treated with topical insecticides.
Pediculosis (lice): Pediculus humanus capitis (head louse); itching, nits on hair; treated with insecticides and nit removal.

Diseases of the Eyes

Bacterial Infections

Conjunctivitis (pinkeye): Most commonly caused by Haemophilus influenzae; red, swollen conjunctiva; treated with topical antibiotics.
Ophthalmia neonatorum: Neisseria gonorrhoeae infection in newborns; can cause blindness; prevented with antibiotic eye drops.
Inclusion conjunctivitis and trachoma: Chlamydia trachomatis; can lead to blindness; spread by contact, flies, fomites.

Protozoan Infections

Acanthamoeba keratitis: Caused by Acanthamoeba spp.; associated with unsanitary contact lenses; can lead to blindness.